Stereotactic radiosurgery for patients with extensive brain metastases across the disease course.

Purpose: Stereotactic radiosurgery (SRS) is the standard of care for patients with limited brain metastases (BM). As systemic therapies prolong survival in metastatic disease, the role of SRS in patients with high intracranial disease burden remains undefined.

Methods: Ninety patients with ≥15 SRS-treated BMs throughout their disease course between 2010 and 2023 were retrospectively reviewed. Outcomes-including overall survival (OS), freedom from whole-brain radiotherapy (FFW), intracranial control (IC), radiation necrosis (RN), and cumulative brain dose-were analyzed. Outcomes were estimated using the Kaplan-Meier method or Fine-Gray model. Univariable and multivariable regression identified prognostic factors.

Results: The median number of BMs treated was 18 (IQR, 16-23) over a median of two SRS courses (IQR, 2-3). Primary tumor sites were lung (47.3%) and breast (22.6%). At initial SRS, 84.9% had ECOG ≤1/KPS > 70, and 33% had neurologic symptoms. With median follow-up of 15 months (range, 0-118), RN occurred in 8.9%; 13.3% developed leptomeningeal disease (median onset 12 months) with a higher risk observed in breast cancer (OR 4.20, 95% CI 1.19-14.87, p = 0.026). The mean cumulative whole-brain dose across all SRS courses was 5.3 Gy. One-year FFW was 75.1% and 68.8% did not undergo WBRT. Median OS was 17 months (95% CI 9.46-24.54), with 1-year OS of 64%.

Conclusions: SRS is safe and feasible for patients with a high BM burden, offering potential delay and avoidance of WBRT. Prospective, multi-institutional studies are warranted to validate these findings and further define the role of SRS in this population.